Sodium hydride → HCID 22347164, compound

HRID 897987Notes

Reaction equation

HRID 897987 reaction equation
O(C1C=CC(C2C3C(=NC=NC=3N)NN=2)=CC=1)C1C=CC=CC=1.[H-].[Na+].BrC1C=CC([N+]([O-])=O)=NC=1.[N+:36]([C:39]1[N:44]=[CH:43][C:42]([N:45]2[C:49]3=[N:50][CH:51]=[N:52][C:53]([NH2:54])=[C:48]3[C:47]([C:55]3[CH:60]=[CH:59][C:58]([O:61][C:62]4[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=4)=[CH:57][CH:56]=3)=[N:46]2)=[CH:41][CH:40]=1)([O-])=O.[H][H]>CN1C(=O)CCC1.C(O)C.[Pd].CN(C)C=O>[NH2:36][C:39]1[N:44]=[CH:43][C:42]([N:45]2[C:49]3=[N:50][CH:51]=[N:52][C:53]([NH2:54])=[C:48]3[C:47]([C:55]3[CH:56]=[CH:57][C:58]([O:61][C:62]4[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=4)=[CH:59][CH:60]=3)=[N:46]2)=[CH:41][CH:40]=1

Participants

10

Reactant 5

HCID 24758Sodium hydride2×HCID 8176205-Bromo-2-nitropyridineHCID 22347268HCID 22347268, compoundHCID 178418361HCID 178418361, compoundHCID 178508717HCID 178508717, compound

Product 1

HCID 22347164HCID 22347164, compound

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 6228DimethylformamideSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of 3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.200 g, 0.00079 mol) in N-methyl pyrrolidinone (10 mL) was reacted with 60% sodium hydride in oil (0.032 g, 0.00079 mol). After gas evolution ceased, the mixture was stirred at ambient temperature for 30 minutes, and 5-bromo-2-nitropyridine (0.161 g, 0.00079 mol) was added and heated at 40° C. for 18 hours. Additional 60% sodium hydride in oil (0.032 g, 0.00079 mol) was added and the mixture was stirred an additional 2 hours. The solvent was removed in vacuo and the residue was partitioned between dichloromethane (15 mL) and water (25 mL). The layers were separated and the aqueous layer was extracted with dichloromethane (2×15 mL). The combined organics were washed with brine and dried over magnesium sulfate. The solvent was removed in vacuo and the residue was purified by flash column chromatography on silica using heptane/ethyl acetate (1:2) as an eluent to give two products. The less polar compound, 1-(6-nitro-3-pyridyl)-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine, was suspended in absolute ethanol (10 mL) and N,N-dimethylformamide (5 mL) and 10% palladium on carbon (0.007 g) was added. The mixture was stirred under a balloon atmosphere of hydrogen for 18 hours. The mixture was filtered through pad of Celite® 521, washing with absolute ethanol. The solvent was removed in vacuo to give 1-(6-amino-3-pyridyl)-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.007 g, 0.00002 mol) as a white solid.

Workup

  1. temperatureheated at 40° C. for 18 hours
  2. stirringthe mixture was stirred an additional 2 hours
  3. customThe solvent was removed in vacuo
  4. customthe residue was partitioned between dichloromethane (15 mL) and water (25 mL)
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with dichloromethane (2×15 mL)
  7. washThe combined organics were washed with brine
  8. dry with materialdried over magnesium sulfate
  9. customThe solvent was removed in vacuo
  10. customthe residue was purified by flash column chromatography on silica
  11. customto give two products
  12. filtrationThe mixture was filtered through pad of Celite® 521
  13. washwashing with absolute ethanol
  14. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-3bf3d0401c944779a39717b352ad319d
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

Loading…